Complete remission of a reccurrent mesenteric liposarcoma with rare histological features following the administration of trabectedin.

The present study describes a rare case of a mesenteric liposarcoma that resulted in a complete remission (CR) following treatment with trabectedin (Yondelis®). The patient presented with abdominal pain and fever. An abdominal mass was identified that corresponded to a mixed-type high-grade mesenteric liposarcoma with wide areas of necrosis, areas of dedifferentiation and features of a leiomyosarcoma. Three months after the removal of the first mass, the patient underwent a second laparotomy, followed by treatment with doxorubicin and ifosfamide. Subsequently, the patient was started on therapy with trabectedin and a CR was noted following only four cycles of therapy. The best responses that are reported in the literature for cases of liposarcoma treated with trabectedin are mostly for liposarcomas of the myxoid/round cell type and are mainly partial responses. In the present study, trabectedin was used for the treatment of a mesenteric liposarcoma of mixed morphological features and a CR was achieved.

Validation and comparison of several published prognostic systems for patients with small cell lung cancer.

The aim of the present study was to validate and compare published prognostic classifications for predicting the survival of patients with small cell lung cancer. We pooled data from phase III randomised clinical trials, and used Cox models for validation purposes and concordance probability estimates for assessing predictive ability. We included 693 patients. All the classifications impacted significantly on survival, with hazard ratios (HRs) in the range 1.57-1.68 (all p<0.0001). Median survival times were 16-19 months for the best predicted groups, while they were 6-7 months for the most poorly predicted groups. Most of the paired comparisons were statistically significant. We obtained similar results when restricting the analysis to patients with extensive disease. Multivariate Cox models for fitting survival data were also performed. The HRs for a single covariate were 8.23 (95% CI 5.88-11.69), and 9.46 (6.67-13.50), and for extensive disease were 5.60 (3.13-9.93), 12.49 (5.57-28.01) and 8.83 (4.66-16.64). Concordance probability estimates ranged 0.55-0.65 (overlapping confidence intervals). Published classifications were validated and suitable for use at a population level. As expected, prediction at an individual level remains problematic. A specific model designed for extensive-disease patients did not appear to perform better.

A phase III randomised study of concomitant induction radiochemotherapy testing two modalities of radiosensitisation by cisplatin (standard versus daily) for limited small-cell lung cancer.

BACKGROUND: The purpose of this study was to determine in limited small-cell lung cancer if locoregional irradiation concurrently with induction chemotherapy with cisplatin and etoposide prolongs survival when cisplatin is given daily as a radiosensitiser. PATIENTS AND METHODS: Two-hundred and four eligible patients were randomised between standard radiosensitised induction chemoradiotherapy (arm A) with cisplatin (90 mg/m(2) day 1) plus etoposide and daily radiosensitised induction chemoradiotherapy (arm B) with cisplatin (6 mg/m(2)/day) plus etoposide. Chemotherapy and chest irradiation (39.90 Gy in 15 fractions >3 weeks) both started on day 1. RESULTS: There was no difference in survival between both arms with respective median, 2 and 5 years of 15.5 months, 35% and 18% in arm A and 17.0 months, 38% and 21% in arm B (P = 0.50). Performance status and T status were identified as independent prognostic factors for survival. In terms of local control rate, there was a statistical trend in favour of arm A with 2% only local relapse versus 10% in arm B. Daily cisplatin radiosensitisation was associated with more oesophagitis and thrombopenia but less nephrotoxicity. CONCLUSION: Induction chemoradiotherapy resulted in both arms in good long-term survival, comparable to the best reported results and without improvement by daily cisplatin administration.

Chemotherapy improves low performance status lung cancer patients.

The aim of the present study was to determine the potential benefit of conventional cisplatin-based chemotherapy on patients with advanced nonsmall cell lung cancer (NSCLC) and poor performance status (PS), defined as 60-70 on the Karnofsky scale. Retrospective analysis was carried out of a randomised trial performed in advanced NSCLC where 485 patients received three courses of gemcitabine+ifosfamide+cisplatin induction chemotherapy. Of the patients, 80% had good PS (Karnofsky 80-100) and 20% poor PS. Response rates were 38 and 28%, respectively. Clinical improvement, defined as achieving a good PS during chemotherapy, was observed overall in 25% of the poor PS patients, with rates of 38, 20 and 14%, respectively, in case of response, no change and progression. PS improved more quickly in the responders. Survival of patients with poor PS was significantly worse, but survival of responders was similar, irrespective of the initial poor or good PS. Although nonfatal toxicity was almost similar, there were more toxic deaths (including vascular and cardiac fatalities) in the poor PS patients (9.2 versus 2.1%). In conclusion, combination chemotherapy is associated with clinical improvement in a substantial number of patients with advanced nonsmall cell lung cancer of poor performance status.

Second-line paclitaxel in non-small cell lung cancer initially treated with cisplatin: a study by the European Lung Cancer Working Party.

In the context of a phase III trial comparing in advanced non-small cell lung cancer (NSCLC) sequential to conventional administration of cisplatin-based chemotherapy and paclitaxel, we evaluated the activity of paclitaxel as second-line chemotherapy and investigated any relation of its efficacy with the type of failure after cisplatin. Patients received three courses of induction GIP (gemcitabine, ifosfamide, cisplatin). Non-progressing patients were randomised between three further courses of GIP or three courses of paclitaxel. Second-line paclitaxel was given to patients with primary failure (PF) to GIP and to those progressing after randomisation to further GIP (secondary failure or SF). One hundred sixty patients received second-line paclitaxel. Response rates were 7.7% for PF and 11.6% for SF (P=0.42). Median survival times (calculated from paclitaxel start) were 4.1 and 7.1 months for PF and SF (P=0.002). In multivariate analysis, three variables were independently associated with better survival: SF (hazard ratio (HR)=1.55, 95% confidence interval (CI) 1.08-2.22; P=0.02), normal haemoglobin level (HR=1.56, 95% CI 1.08-2.26; P=0.02) and minimal weight loss (HR=1.79, 95% CI 1.26-2.55; P=0.001). Paclitaxel in NSCLC patients, whether given for primary or for SF after cisplatin-based chemotherapy, demonstrates activity similar to other drugs considered active as second-line therapy.

A phase III randomised trial comparing sequential chemotherapy using cisplatin-based regimen and paclitaxel to cisplatin-based chemotherapy alone in advanced non-small-cell lung cancer.

BACKGROUND: The purpose of this study is to determine whether in advanced non-small-cell lung cancer (NSCLC), the sequential administration of cisplatin-based chemotherapy and paclitaxel (Taxol) is superior to a cisplatin-based chemotherapy, followed by paclitaxel as salvage treatment. PATIENTS AND METHODS: A total of 485 chemotherapy naive patients with advanced NSCLC were treated with three courses of GIP (gemcitibine + ifosfamide + cisplatin), consisting of cisplatin 50 mg/m(2) on day 1, ifosfamide 3 g/m(2) on day 1 and gemcitabine 1 g/m(2) on days 1 and 8. Patients with nonprogressive disease were then randomised to further similar courses of GIP or courses of paclitaxel (225 mg/m(2) over 3 h every 3 weeks). RESULTS: Objective response or nonprogression after induction GIP occurred in 174 and 115 patients, respectively. After randomisation, there were 140 patients in the GIP arm and 141 in the paclitaxel arm. In terms of postrandomisation survival, there was no statistically significant difference (P = 0.17) between the two arms. Median times were 9.7 [95% confidence interval (CI) 7.8-11.6] and 11.9 (95% CI 9.4-14.3) months for paclitaxel and GIP, respectively. Multivariate analysis demonstrated that sex and haemoglobin were independent prognostic factors. After adjustment for these factors, the observed hazard ratio was 0.81 (95% CI 0.63-1.04) in favour of GIP (P = 0.10). Toxicity was tolerable; there was a significantly higher rate of grades III/IV thrombocytopenia with GIP and more alopecia with paclitaxel. CONCLUSION: Sequential chemotherapy using cisplatin-based regimen followed by paclitaxel does not result in better outcome than cisplatin-based chemotherapy using taxane as salvage treatment.

First-line chemotherapy with docetaxel and cisplatin in metastatic breast cancer.

The purpose of this study was to evaluate the efficacy and tolerance of combined treatment with docetaxel-cisplatin as first-line chemotherapy in patients with metastatic breast cancer (MBC). Consecutive eligible chemonaive patients received docetaxel 75 mg/m(2) on day 1 and cisplatin 75 mg/m(2) on day 2 every 3 weeks for 6 cycles, with prophylactic recombinant human granulocyte colony-stimulating factor (rHuG-CSF) on days 4-11. Thirty-two patients (64%) had received prior adjuvant chemotherapy; these included 16 (32%) who had received anthracyclines. In 50 evaluable patients with a median age (range) of 56 (31-72) years, the overall response rate was 68% (95% CI, 55-81%), with 7 (14%) complete and 27 (54%) partial responses. Stable and progressive disease was observed in 10 (20%), and 6 (12%) patients, respectively. The median duration of response was 10 months, and the median time to progression was 39 weeks. Grade 3/4 hematological toxicity included--neutropenia in 9 patients (18%), anemia in 2 (4%) and thrombocytopenia in 1 (2%). One patient (2%) with febrile neutropenia required hospitalization. Grade 3/4 nonhematological toxicities included nausea/vomiting in 18%, nephrotoxicity in 14%, asthenia (4%), and neurotoxicity (2%). Toxicity was common in older patients (>56 years). There were no treatment-related deaths. A combination of docetaxel-cisplatin with rHuG-CSF support is well tolerated and effective as first-line chemotherapy in MBC.

Survival is better predicted with a new classification of stage III unresectable non-small cell lung carcinoma treated by chemotherapy and radiotherapy.

UNLABELLED: The 1997 International staging system (ISS) classification separated stage III non-small cell lung cancer (NSCLC) into stages IIIA and IIIB. In a previous study including unresectable NSCLC initially treated with chemotherapy, we analysed survival according to tumour (T) and node (N) stages and derived a classification into stages IIIbeta (T3-4N3) and IIIalpha (other TN stage III) that had a better discrimination on survival distribution. The aim of this study was to validate these results in a further set of patients. Patients with unresectable stage III NSCLC included in a phase III trial assessing the role of increased dose chemotherapy (SuperMIP: mitomycin 6 mg/m2, ifosfamide 4.5 g/m2, cisplatin 60 mg/m2, carboplatin 200 mg/m2) in comparison to standard chemotherapy MIP (mitomycin 6 mg/m2, ifosfamide 3 g/m2, cisplatin 50 mg/m2), before thoracic irradiation (60 Gy in 30 fractions over 6 weeks) were the subject of this study. Survival distributions were assessed by the method of Kaplan-Meier. Survival comparisons were made by the log-rank test. Multivariate analyses using Cox regression models, included all potential prognostic factors for survival with a P-value <0.2 in univariate analysis. According to the 1997 International staging system classification, 328 eligible patients were included in the study. There was no imbalance between the two arms. Five parameters were significantly associated (P < or = 0.05) with survival in univariate analysis: European lung cancer working party (ELCWP) staging (IIIalpha[n = 294 pts] versus IIIbeta [n = 46]), Karnofsky index, weight loss, platelet count and haemoglobin level. These variables as well as the 1997 ISS staging, white blood cell (WBC) count, LDH and sodium levels were included in a multivariate analysis. Two models were constructed, including either the ELCWP or the 1997 ISS. In model 1 (ISS included), Karnofsky index (HR 0.69; 95% confidence interval (CI) 0.47-1.00; P = 0.05) and haemoglobin (HR 1.49; 95% CI 1.11-1.99; P = 0.007) were found significant. In model 2, including ELCWP staging, two variables were associated with survival: ELCWP staging (HR 1.68; 95% CI 1.20-2.35; P = 0.002) and haemoglobin (HR 1.54; 95% CI 1.15-2.07; P = 0.01). CONCLUSION: In initially unresectable stage III NSCLC treated by chemotherapy and radiotherapy, we validated the results of our previous study. The classification into stages IIIbeta (T3-4N3M0) and IIIalpha (other TN stage III) better discriminates the patients in term of survival than the 1997 ISS classification.

A phase III randomised study comparing two different dose-intensity regimens as induction chemotherapy followed by thoracic irradiation in patients with advanced locoregional non-small-cell lung cancer.

PURPOSE: The aim of this study was to determine the role of chemotherapy dose intensity in patients with initially unresectable non-metastatic non-small-cell lung cancer (NSCLC), with survival as primary end point, by testing two different regimens as induction chemotherapy followed by thoracic irradiation. PATIENTS AND METHODS: Patients had pathologically proven NSCLC, an initially unresectable non-metastatic tumour without homolateral malignant pleural effusion, no prior history of malignancy and had received no prior therapy. Treatment was randomised for chemotherapy between three courses of MIP (mitomycin C 6 mg/m2; ifosfamide 3 g/m2; cisplatin 50 mg/m2) or SuperMIP (mitomycin C 6 mg/m2; ifosfamide 4.5 g/m2; cisplatin 60 mg/m2, carboplatine 200 mg/m2), followed by chest irradiation (60 Gy; five times per week, for 6 weeks). If the tumour became resectable after chemotherapy, surgery was performed, followed by mediastinal irradiation. RESULTS: A total of 351 patients were eligible: 176 in the MIP arm and 175 in the SuperMIP arm, with 43% and 51% stages IIIA and IIIB, respectively. There was a significantly higher objective response rate with SuperMIP (46%) compared with MIP (35%) (P=0.03) [95% confidence interval (CI) for the difference between the response rates, 1% to 22%]. After induction chemotherapy, surgery was performed in 54 (15%) patients (27 per arm) and chest irradiation in 203 (57%) patients (102 in the MIP arm and 101 in the SuperMIP). In terms of survival, there was no statistically significant difference between the two study arms (P=0.16), with median survival times of, for MIP and SuperMIP, respectively, 12.5 (95% CI 10.1-14.9) and 11.2 (95% CI 9.7-12.8) months. Haematological toxicity and dosage reductions were higher with SuperMIP, which was nevertheless associated with a significantly increased absolute dose intensity. CONCLUSIONS: High dose-intensity induction chemotherapy does not improve survival in initially unresectable non metastatic NSCLC.

Vinorelbine and cisplatin for metastatic breast cancer: a salvage regimen in patients progressing after docetaxel and anthracycline treatment.

PURPOSE: To assess the antitumor efficacy and safety of a combination of vinorelbine (VNR) and cisplatin in patients with metastatic breast cancer previously treated with anthracyclines and docetaxel. PATIENTS AND METHODS: Thirty-six patients with assessable metastatic breast cancer previously treated with anthracyclines and docetaxel (adjuvant n = 1, palliative n = 20, both n = 15) were studied. Cisplatin was given at 75 mg/m2 on day 1 followed by 25 mg/m2 VNR on days 1 + 8 in a 5-minute i.v. infusion. Courses were repeated every 3 weeks. Treatment was continued until disease progression, excess toxicity, or patient refusal. Patients were classified according to their response to anthracyclines according to criteria published previously: 1) Anthracycline and/or docetaxel resistant were patients who progressed during treatment with anthracyclines and docetaxel or within 4 months after cessation of treatment (metastatic). In addition, adjuvant patients who progressed within 6 months after completion of chemotherapy belong to this group. 2) Anthracycline and/or docetaxel relapsed were either metastatic patients who responded initially and then progressed after 4 months of completing an anthracycline- and docetaxel-based chemotherapy or patients who progressed after 6 months from completion of anthracycline/docetaxel-based adjuvant chemotherapy. RESULTS: Two patients (5.6%) achieved a complete response (CR) and 15 patients (41.6%) achieved a partial response (PR), for an overall response rate (OR) of 47.2% (95% confidence interval, 31-63). Of 18 patients relapsed to anthracycline/docetaxel, 2 had a CR (11%) and 8 a PR (44.4%), giving an objective response of 55.5%. Stable disease (SD) was observed in one patient (5.5%); seven patients had progressive disease (PD) (39%). Among the 18 resistant patients, 7 PRs (39%) were observed (p = 0.5), one patient (5.5%) had stable disease, 10 patients (55.5%) progressed. The median time to progression (TTP) was 16 weeks and median overall survival 36 weeks. Relapsed patients had a longer TTP than resistant patients (24 vs. 8 weeks, p = 0.05) but similar survival (48 vs. 24 weeks, p = 0.173). All patients were assessed for toxicity. The main toxicity was neutropenia grade 3 and 4 in 47% of patients. Febrile neutropenia requiring hospitalization was absent. There were no treatment-related deaths. Thrombocytopenia grade 3 and 4 occurred in four patients (11%). Phlebitis, orthostatic hypotension, and asthenia, all reversible, were observed in 3% of patients, respectively. CONCLUSION: This cisplatin/VNR regimen is well tolerated and active in patients who failed anthracyclines and docetaxel treatment. The response rate, TTP, and survival data are high and indicate that cisplatin/VNR may have a place as salvage treatment in this group of patients. If these results can be verified in multi-institutional trials, this combination of drugs would merit investigation as part of a first-line therapy in breast cancer.

Vinorelbine and docetaxel as first-line chemotherapy in metastatic breast cancer.

PURPOSE: To evaluate the efficacy and tolerability of a combination of vinorelbine (VNR) and docetaxel (DOC) as first-line chemotherapy in patients with metastatic breast cancer. PATIENTS AND METHODS: The study group comprised 40 women with untreated metastatic breast cancer with visceral (85%) and bone (70%) metastases. Of the 40 patients, 24 (60%) had previously received adjuvant chemotherapy, which had included anthracyclines in 12 patients (30%). Treatment consisted of VNR 25 mg/m(2) on days 1 and 5, and DOC 75 mg/m(2) on day 1 every 3 weeks. Depending on the neutrophil nadir (grade 3 or 4 neutropenia by WHO criteria) recombinant human granulocyte colony-stimulating factor (G-CSF) 5 micro g/kg on days 2-4 and 6-13 was given for all subsequent treatment cycles. RESULTS: The overall response rate (ORR) was 40% (95% confidence interval, CI 15-65). Six patients (15%) achieved a complete response (CR) and ten patients (25%) achieved a partial response (PR). Stable disease (SD) was observed in six patients (15%), and 18 patients (45%) had progressive disease (PD). The median duration of response was 8 months and the median predictive time to progression (TTP) was 6 months. The main toxicity was neutropenia grade 3 and 4 in 28 patients (70%). Febrile neutropenia requiring hospitalization occurred in 12 patients (30%). Grade 3 or 4 anemia was seen in two patients (5%) and grade 3 or 4 thrombocytopenia was seen in one patient (2.5%). Severe nonhematologic toxicity, except alopecia, was uncommon and included stomatitis in two patients (5%), vomiting in two (5%) and diarrhea in one (2.5%). There were no treatment-related deaths. CONCLUSIONS: The combination of VNR and DOC at the doses used in this study showed moderate activity as first-line chemotherapy in metastatic breast cancer. Neutropenia was considerable despite G-CSF administration.

A phase II randomised trial comparing the cisplatin-etoposide combination chemotherapy with or without carboplatin as second-line therapy for small-cell lung cancer.

BACKGROUND: A phase II randomised trial was performed with patients with SCLC to determine if the addition of carboplatin to cisplatin-etoposide might improve the response rate in second-line therapy. PATIENTS AND METHODS: Sixty-five eligible patients were randomised: 31 for CE (cisplatin 20 mg/m(2) and etoposide 100 mg/m(2) on days 1-3) and 34 for CCE (carboplatin 200 mg/m(2) on day 1, cisplatin 30 mg/m(2) on days 2-3, etoposide 100 mg/m(2) on days 1-3). RESULTS: Eighty-two per cent of these patients had an objective response to first-line therapy and, among responders, 63% had a treatment-free interval of >3 months after previous therapy. The best response rates were 29% [95% confidence interval (CI) 13-45] and 47% (95% CI 30-64) for CE and CCE, respectively, with median survival times of 4.3 and 7.6 months. Dose-intensity analysis revealed a significant improvement in the relative dose-intensity and etoposide absolute dose-intensity for CE. Toxicity was tolerable and comparable between the two study arms. CONCLUSION: CCE appears to be associated with a high objective response rate. The phase II randomised study design suggests that a comparison between the two regimens in a phase III trial would be interesting, but will probably be difficult to perform for reasons of accrual.

A three-arm phase III randomised trial comparing combinations of platinum derivatives, ifosfamide and/or gemcitabine in stage IV non-small-cell lung cancer.

OBJECTIVE: To determine, in stage IV non-small-cell lung cancer (NSCLC), if the combination of gemcitabine-a new active drug-with ifosfamide (IG) or with the cisplatin-carboplatin association (CCG) will improve survival (primary end point) in comparison with a first-generation regimen, cisplatin-carboplatin-ifosfamide (CCI). PATIENTS AND METHODS: A total of 284 chemotherapy-naïve patients with metastatic NSCLC were randomised. Four were ineligible and 16 were not assessable for responses. Cisplatin was given at 60 mg/m2 on day 1, carboplatin AUC 3 mg.min/ml on day 1, ifosfamide 4.5 g/m2 on day 1 and gemcitabine 1 g/m2 on days 1, 8 and 15. Courses were repeated every 4 weeks. Response was assessed after three courses and chemotherapy was continued in responding patients until best response. There were 94 eligible patients in the CCI arm, 92 in CCG and 94 in the IG arm. RESULTS: The objective response rates for CCI, CCG and IG were 23% [95% confidence interval (CI) 15% to 32%], 29% (95% CI 20% to 39%) and 25% (95% CI 16% to 33%), respectively ( P = 0.61). Median survival time was 24, 34 and 30 weeks, respectively (P = 0.20). One-year survival was 23, 33 and 35%, and 2-year survival was 11, 14 and 17%, respectively. In some subgroups (older patients, women), there was a significant survival advantage for CCG and IG compared with CCI. Toxicity was tolerable: severe alopecia was less frequent in the CCG arm, and IG was associated with significantly more thrombopenia while CCG was associated with more leucopenia. CONCLUSION: In stage IV NSCLC, treatment with regimens including the new drug gemcitabine were associated with a better but not statistically significant observed survival compared with a classical first-generation cisplatin-containing regimen. The non-platinum combination of gemcitabine was as effective as its combination with platinum.

Control of irinotecan-induced diarrhea by octreotide after loperamide failure.

Diarrhea is a well-recognized side effect of chemotherapy, which affects the quality of life and when refractory is potentially life threatening. Irinotecan (CPT-11) is associated with an elevated incidence of chemotherapy-induced diarrhea and subsequent morbidity. Standard antidiarrheal treatment is based on high-dose loperamide, but this agent is associated with a significant failure rate. Octreotide is active against chemotherapy-induced diarrhea caused by fluoropyrimidines and irinotecan, with a distinct mechanism of action. We administered octreotide in a phase I trial in 37 patients who received irinotecan and experienced loperamide-refractory diarrhea, 23 of whom experienced grade III-IV diarrhea and were treated with loperamide. The 13 patients in whom to loperamide failed to control diarrhea received octreotide, with a high response rate (92%). We conclude that octreotide is effective against loperamide-refractory diarrhea resulting from irinotecan-based chemotherapy.

Prevention of vinorelbine phlebitis with cimetidine. A two-step design study.

One hundred eighteen patients with various malignancies received a total of 847 vinorelbine (VNR) infusions, during 25 of which episodes of vinorelbine phlebitis occurred (1 in each of the 25 patients concerned). Venous irritation was graded with reference to the scale devised by Rittenberg et al. To prevent these 25 patients against further venous toxicity, we pretreated them with cimetidine 200 mg i.v. prior to VNR administration in subsequent cycles of chemotherapy. In most (19, or 76%) complete prevention of recurrent phlebitis was observed, while partial prevention was observed in 5 patients (20%). Treatment was unsuccessful in 1 patient. In 127 VNR infusions given after cimetidine prophylaxis only 7 (6%) episodes of phlebitis occurred. These data show that i.v. administration of cimetidine prior to vinorelbine infusion can successfully prevent recurrence of phlebitis in patients who have shown venous irritation upon prior VNR treatment, at a rate of 94%.

Dose-intensive epirubicin-based chemotherapy is superior to an intensive intravenous cyclophosphamide, methotrexate, and fluorouracil regimen in metastatic breast cancer: a randomized multinational study.

PURPOSE: To determine the relative efficacy of a cyclophosphamide epirubicin and fluorouracil (CEF) regimen compared with an intravenous (IV) cyclophosphamide, methotrexate, and fluorouracil (CMF) combination in metastatic breast cancer. PATIENTS AND METHODS: Patients were randomized to receive either CEF (cyclophosphamide 400 mg/m(2) IV, epirubicin 50 mg/m(2) IV, and fluorouracil 500 mg/m(2) IV on days 1 and 8), or CMF (cyclophosphamide 500 mg/m(2) IV, methotrexate 40 mg/m(2) IV, and fluorouracil 600 mg/m(2) IV on days 1 and 8). Treatment was given in 3- to 4-week cycles for a total of six to nine cycles. RESULTS: A total of 460 patients (223 CEF and 237 CMF) were randomized. Overall response rate was superior for CEF than CMF in all randomized patients (57% v 46%, respectively; P =.01) and in the assessable subset (66% v 52%, respectively; P =.005). With a median follow-up of more than 20 months, time to progression (TTP) was significantly longer with CEF than CMF (median 8.9 v 6.3 months, respectively; P =.0064), as was time to treatment failure (TTF) (median 6.2 v 5.0 months, respectively; P =.01). Significant survival differences were not observed between CEF and CMF (median 20.1 v 18.2 months, respectively; P =.23). Granulocytopenia and infections were similar in both arms. Grade 3/4 nausea/vomiting and alopecia were more frequent with CEF, whereas diarrhea was more frequent with CMF. Cardiac toxicity, primarily asymptomatic, required withdrawal from study of 15 patients on CEF (7%) and one patient on CMF. CONCLUSION: This CEF regimen safely provides significantly better tumor control than CMF, manifest as a higher response rate, and longer TTP and TTF, but not survival, when used as first-line chemotherapy for metastatic breast cancer.

Vinorelbine and cisplatin in metastatic breast cancer patients previously treated with anthracyclines.

PURPOSE: To assess the antitumor efficacy and safety of a vinorelbine and cisplatin combination in patients with metastatic breast cancer previously treated with anthracyclines. PATIENTS AND METHODS: Fifty-three patients with assessable metastatic breast cancer with previous exposure to anthracyclines (adjuvant n = 6, palliative n = 47) were studied. Cisplatin 75 mg/m2 on day 1 was given followed by 25 mg/m2 vinorelbine (VNR) on days 1 + 8, in a five-min i.v. infusion. Courses were repeated every three weeks on an outpatient basis. Treatment continued until disease progression, excess toxicity or patient refusal. Patients were classified according to their response to anthracyclines: anthracycline refractory patients were patients who had never responded under an anthracycline regimen. Anthracycline resistant patients were either metastatic patients who progressed within four months of completing anthracycline-based chemotherapy or patients who progressed within six months of completion of an anthracycline adjuvant treatment. Patients who progressed four months after the end of an anthracycline regimen in metastatic setting or six months after the end of an anthracycline regimen in adjuvant setting were considered as patients previously treated with anthracyclines and were called 'relapsed'. RESULTS: Four patients (8%) achieved a complete response (CR) and twenty-two patients (41%) achieved a partial response (PR) with an overall response rate (OR) of 49% (95% confidence interval (CI): 35-63). Stable disease (SD) was observed in five patients (9%), twenty-two patients had progressive disease (PD). Responses according to previous sensitivity to anthracycline were as follow: 5 refractory patients achieved a PR from 14 patients (36%). Seven of sixteen resistant patients responded (44%), six with PR and one with CR. Among 23 'relapsed' patients, 14 responses were observed (61%), with 3 CR and 11 PR. There was no statistical difference in RR among the three groups. The median duration of response for all patients was 7 months, the median time to progression (TTP) 5 months and median overall survival 12 months. All patients were assessed for toxicity. The main toxicity was neutropenia grade 3 and 4 in 49% of patients. Febrile neutropenia requiring hospitalization was uncommon (2 patients). There were no treatment related deaths. Despite potential overlapping neurologic toxicities of the two drugs, only eight patients (15%) developed neuropathy, which was, however, mild (grades 1 and 2). CONCLUSIONS: This cisplatin VNR regimen is well tolerated and active in patients who failed anthracyclines. The response rate, TTP and survival data are encouraging and indicate that cisplatin VNR may have a place as second-line treatment alternative to taxanes or other less active regimens. If these results can be verified in multi-institution trials, this combination of drugs would merit investigation as first-line therapy in this patient population.

A phase II trial testing gemcitabine as second-line chemotherapy for non small cell lung cancer. The European Lung Cancer Working Party. 101473.1044@compuserve.com.

The purpose of the present trial was to determine the activity of gemcitabine as a second-line chemotherapy for non small cell lung cancer (NSCLC). To be eligible, patients had to have pathologically proven NSCLC that has failed to respond to a first-line chemotherapy with a cisplatin-containing regimen, a Karnofsky performance status greater than 50 and adequate renal, haematological and hepatic functions. After registration, patients were treated by gemcitabine given i.v. at a dose of 1 g/m(2) on days 1, 8, 15 every 4 weeks. Response was assessed after two courses of therapy. Eighty-two patients have been registered, five are ineligible and 65 are assessable for response. Four partial responses were observed (6%). No change was documented in 18 cases (28%). Tolerance was good. A few grade III leucopenia and grade III-IV thrombopenia were observed. We conclude that gemcitabine has a modest activity as second-line chemotherapy for NSCLC. It has the advantage to be well tolerated and may thus be one drug to be proposed to the patients who have disease progression after a first-line chemotherapy and who ask for further treatment.

A phase II study of the effectiveness of docetaxel (Taxotere) in women with advanced breast cancer previously treated with polychemotherapy. Hellenic Cooperative Interhospital Group in Oncology.

PURPOSE: The aim was to study the effectiveness of docetaxel (Taxotere) in patients with advanced breast cancer treated previously with polychemotherapy. PATIENTS AND METHODS: Forty-nine patients received docetaxel (100 mg/m2; 1-h i.v. infusion) and corticosteroid premedication. Forty-one patients who had received previous anthracycline treatment were divided into anthracycline-refractory and anthracycline-resistant (early and late) groups. RESULTS: Of 45 evaluable patients, 66.7% had a partial response (PR) and 2.2% a complete response (CR), giving an overall response rate (ORR) of 68.9%. The ORR in anthracycline-refractory patients was 60% versus 82.6% in anthracycline-resistant patients; the difference was not significant. The ORR in early-resistance patients was 62.5% versus 93.4% in late-resistance patients (0.05 < P < 0.1). The median response duration and overall survival was 8 months (range, 4-23 + months) and 11.5 months (range, 4-31 + months), respectively, in 39 patients treated previously for metastatic disease. For 295 courses, grade 3/4 neutropenia developed in 28.6% of patients (12.5% of courses) and was febrile in 26.5% of patients (6.1% of courses), including one septic death. Hypersensitivity reactions (HSR) developed in 16.3% of patients, and fluid retention developed in 34.7% of patients (11.9% of courses). CONCLUSIONS: Docetaxel is an active second-line drug in advanced breast cancer. The time of relapse after cessation of anthracycline treatment may be a significant prognostic factor.